JP2014525589A - Measuring device with sensor array - Google Patents

Abstract

A system for obtaining PH measurements includes a disposable probe and a reader. The disposable probe includes a plurality of indicator electrodes and at least one reference electrode. The reader is configured to operably engage the disposable probe and provide pH information for the sample. In one embodiment, the disposable probe further comprises a plurality of controllable orifices. In one embodiment, the first orifice is constructed and arranged to provide a first fluid path to the first indicator electrode, and the second orifice provides a fluid path to the second indicator electrode. Has been constructed and sequenced.

Description

(Citation of related application)
This application is related to US Provisional Patent Application No. 61 / 531,546 (filed Sep. 6, 2011, Clark, et al., “MESUREMENT DEVICE WITH READER AND DISPOSABLE PROBE”). The disclosure of that application is incorporated by reference in its entirety.

  The following information is provided to assist the reader in understanding the techniques described below and certain environments in which such techniques can be utilized. The terminology used herein is not intended to be limited to any particular narrow interpretation unless explicitly stated otherwise herein. The technical literature described herein can facilitate understanding of the technology and its background. All technical literature cited herein by reference is incorporated herein by reference in its entirety.

  A typical pH sensor using the potential difference principle includes a reference electrolyte, an indicator electrode immersed in or in contact with a sample solution (the pH of the sample solution is measured), and a reference electrolyte. And a measurement value circuit in electrical connection with the reference electrode and the indicator electrode, for example, a potential difference circuit. The potential difference circuit measures the potential difference between the indicator electrode and the reference electrode. Electrical connection between the electrodes is possible by ionic contact between the electrolyte in which the indicator and reference electrodes are immersed. The pH value of the sample or analyte electrolyte (which is proportional to the concentration of hydrogen ions in the sample electrolyte) is directly correlated with the potential difference generated at the indicator electrode according to the Nernst equation.

  In the above-described configuration, the important condition for accurate measurement is that the potential difference generated between the reference electrode and the reference electrolyte is kept constant, and the reading from the potential difference circuit is only the potential difference at the indicator electrode, that is, The purpose is to represent only the pH in the electrolyte. In order to satisfy this condition, the general configuration is to immerse the reference electrode in the saturated reference electrolyte and provide a small “window” positioned between the saturated reference electrolyte and the sample or analyte electrolyte. Thus, ionic contact between the saturated reference electrolyte and the sample or analyte electrolyte, and thus electrical connection, is provided. The “window” is usually made of a porous material, such as a porous glass membrane, a hydrophilic porous polymer membrane or the like. The porosity of the “window” causes a non-negligible mass transfer between the saturated reference electrolyte and the sample or analyte electrolyte, thereby causing cross-contamination of both electrolytes.

  Dilution of the saturated reference electrolyte caused by such contamination can be a major problem because it changes the potential difference of the reference electrode. Contamination also degrades the stability of the pH sensor and shortens the life of the pH sensor. The problem is that the volume of the saturation reference electrolyte is very small compared to the sample electrolyte because the size of the pH sensor is reduced (eg, to very small, micro-level, microscale, or smaller) So it gets worse. For example, in applications where a microscale or smaller pH sensor is implanted in the human body and used to measure physiological pH (eg, myocardial pH), the volume of the saturated reference electrolyte is measured by the pH. It is extremely small compared to the volume of myocardial tissue. On such a scale, the saturated reference electrolyte is diluted much more rapidly than in the case of a macroscale glass tube pH sensor. Another factor that adversely affects the useful life of pH sensors, eg, microscale pH sensors, is the durability of the reference electrode. In many cases, the conductive material of the reference electrode gradually dissolves and is consumed in the saturated reference electrolyte. At some point during the dissolution and consumption of the reference electrode, the useful life of the pH sensor ends.

  According to a first aspect of the inventive concept, a system for obtaining pH measurements is disclosed. The system includes a disposable probe and a reader. The disposable probe includes a plurality of indicator electrodes and at least one reference electrode. The reader is constructed and arranged to operably engage the disposable probe and provide pH information about the sample.

  In some embodiments, the disposable probe has a first controllable orifice constructed and arranged to provide a first fluid path to the first indicator electrode, and a first to the second indicator electrode. A plurality of controllable orifices, such as a second controllable orifice, constructed and arranged to provide two fluid paths. In an alternative embodiment, the first controllable orifice is constructed and arranged to provide a fluid path to the first indicator electrode, and the second controllable orifice is the first control electrode to the first reference electrode. Constructed and arranged to produce two fluid paths.

  The system may include an electronics module configured to actuate one or more controllable orifices, such as electronics module, positioned in the reader. The reader may comprise a user interface configured to communicate with the electronics module, such as displaying pH information and allowing information to be entered by the system operator. The electronic module may include memory and other electronic microcontroller components. These components continuously transition from one controllable orifice to another controllable orifice, such as to selectively open a fluid path to the first electrode, then the second electrode, etc. (E.g., through the use of a lookup table stored in memory). The fluid path can be fluidly connected to one or more solutions, such as a reference solution and / or a sample solution, so that fluid can be operatively delivered to an electrode, such as an indicator electrode and / or a reference electrode.

  In some embodiments, the controllable orifice comprises a membrane, such as a multilayer membrane. When the heating element is actuated (eg, by a mechanical force generated by a temperature change), the heating element may be in, on or close to, such as to rupture or otherwise open the film. Can be positioned. The heating element may comprise a coil configured to heat as current is passed through it, such as a coil made of gold and / or chromium or other metal. The inventive membrane and / or heating element can be made by MEMS or other automated and / or layered manufacturing processes.

  The indicator electrode of the inventive concept may comprise an iridium oxide electrode. The disposable probe can include a plurality of indicator electrodes, such as at least nine, at least 30, or at least 90 indicator electrodes. In one embodiment, the disposable probe comprises three or more indicator electrodes and at least two reference electrodes. The reference electrode can comprise a silver-silver chloride electrode and / or an iridium oxide electrode.

  The indication of the inventive concept and / or the reference electrode may be surrounded by a walled chamber. The chamber may comprise a vacuum chamber (eg, a chamber with an environment in full or partial vacuum), such as for drawing a solution such as a sample solution into the chamber. Alternatively, one or more vents may be in fluid communication with the chamber, such as to improve the inflow of fluid, such as sample fluid, into the chamber. The chamber can comprise a hydrophilic material and / or can include a coating, such as a hydrophilic coating. Alternatively or additionally, the walls of the chamber can be constructed and arranged differently to draw the solution into the chamber or otherwise improve the flow of the solution into it (e.g., the gradient is Attached).

  An indication of the inventive concept and / or a reference electrode can be mounted on a substrate with or without a mounting pad such as a titanium mounting pad. An indication of the inventive concept and / or a reference electrode may be made by MEMS or other automated and / or layered manufacturing processes.

  A disposable probe of the inventive concept may include a liquid boundary, and a cap may be included to prevent drying of the liquid boundary and / or alternatively to protect the distal end of the disposable probe. A reference solution such as a potassium chloride (KCL) reference solution may be included in the system. One or more components of the system, such as the indicator or reference electrode, can be mounted on a substrate, such as a glass, silicon, or plastic substrate. Numerous combinations of two or more indicator electrodes and one or more reference electrodes can be mounted on the substrate.

  The inventive system includes one or more sensors, such as one or more sensors used by the electronics module of the system to determine pH readings and / or to assist in the calibration of pH readings. The above sensors can be included. Exemplary sensors include, but are not limited to, pressure sensors, humidity sensors, and combinations thereof. In one embodiment, the sensor is included in the reader. Alternatively or additionally, the sensor can be included in a disposable probe.

  In an exemplary embodiment, the system of the present invention includes a plurality of disposable probes, each constructed and arranged to operably engage a reader.

  The techniques described herein, together with their attributes and attendant advantages, will be best understood by considering the following detailed description, taken in conjunction with the accompanying drawings. In the accompanying drawings, representative embodiments are described as examples.

FIG. 1 illustrates a top view of an embodiment of a pH sensor. FIG. 2 illustrates a cross-sectional view of the pH sensor of FIG. 1 along A-A 'illustrated in FIG. FIG. 3 illustrates a cross-sectional view of another pH sensor embodiment. FIG. 4 illustrates a cross-sectional view of another pH sensor embodiment. FIG. 5 illustrates a top view of an embodiment of a system comprising a disposable probe and reader. FIG. 6 illustrates a schematic diagram of an array of sensors. FIG. 6a illustrates a top view of the controllable orifice. FIG. 7 illustrates a cross-sectional view of an array of sensors. FIG. 7a illustrates a cross-sectional view of the array of FIG. 7 after the actuation process has occurred. FIG. 8 illustrates a cross-sectional view of another embodiment of an array of sensors. FIG. 8a illustrates a cross-sectional view of the array of FIG. 8 after the actuation process has occurred. FIG. 9 illustrates a process for manufacturing an array of sensors. FIG. 10 illustrates a cross-sectional view of another embodiment of an array of sensors. FIG. 10a illustrates a cross-sectional view of the array of FIG. 10 after the first orifice has been opened. FIG. 10b illustrates a cross-sectional view of the array of FIG. 10 after the second orifice has been opened. FIG. 10c illustrates a cross-sectional view of an array of sensors comprising a plurality of indicator electrodes and a plurality of reference electrodes.

  Reference will now be made in detail to embodiments of the present technology, examples of which are illustrated in the accompanying drawings. The same reference numbers are used throughout the drawings to refer to the same or like parts.

  As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include the plural unless the context clearly dictates otherwise. Thus, for example, reference to “a bubble” includes a plurality of such bubbles and equivalents known to those skilled in the art, and the like, and the description “the bubbles” is one or Two or more such foams and foam equivalents known to those skilled in the art, and so on.

  Further, as used herein, the words “comprising” (and any form of comprising such as “comprise” and “comprises”), “having” (and any Any form such as “have” and “has”), “including” (and any form of inclusion such as “includes” and “include”), or “containing” (and (Any form of continging, such as “contains” and “contain”) defines the presence of the stated feature, integer, step, action, element, and / or component, but one or more other features, Integer, step, action, element, structure Elements, and / or it will be understood that it is not intended to exclude the presence or addition of groups thereof.

  The terms “first”, “second”, “third”, etc. may be used herein to describe various limits, elements, components, regions, layers, and / or compartments, It will be understood that these limits, elements, components, regions, layers and / or compartments should not be limited by these terms. These terms are only used to distinguish one limit, element, component, region, layer or section from another limit, element, component, region, layer or section. Accordingly, the first limit, element, component, region, layer, or section discussed below is also referred to as the second limit, element, component, region, layer, or section without departing from the teaching of the present application. Can be done.

  In addition, one element is referred to as another element “on” or “attached”, “connected” or “coupled” to it. It should be understood that sometimes intervening elements can be present, which can be directly on or above other elements, or connected or coupled thereto. In contrast, an element is referred to as “directly on”, or “directly connected”, or “directly coupled” to another element. There are no intervening elements. Other words used to describe the relationship between elements should be interpreted in a similar manner (eg, “between” vs. “directly between”, “adjacent”) And “directly adjacent” etc.)). When an element is referred to herein as “over” another element, it can be above or below the other element and can be directly coupled to the other element? Or intervening elements can be present or the elements can be separated by a gap or gap.

  The term “and / or” as used herein should be taken as specific disclosure of each of the two defined features or components, with or without the other. . For example, “A and / or B” is a specific disclosure of each of (i) A, (ii) B, (iii) A and B, each as individually described herein. Should be taken as

  FIG. 1 is described in International Patent Application No. PCT / US2010 / 045847, the contents of which are incorporated herein by reference in their entirety, such as microscale or smaller (eg, nanometers). FIG. 4 illustrates a top view of pH sensor 10 according to various embodiments that are easily formed to scale dimensions. The term “microscale” when used in connection with the pH sensor herein refers to a sensor having a dimension of less than 1 centimeter. In some embodiments, the dimensions of the pH sensor herein can be subjected to micro and / or nano fabrication techniques. In some embodiments, the reference electrolyte volume was 20 cubic mm or less.

  FIG. 2 illustrates a cross-sectional view (taken along line A-A ′ illustrated in FIG. 1) of the pH sensor 10. In some embodiments, the pH sensor 10 may be sized and configured to allow its implantation into the body (ie, a human or animal) using, for example, minimally invasive techniques. it can. In some embodiments, the length, width, and height of the pH sensor were each less than 1 centimeter. Such a microscale pH sensor 10 can be used in various applications for measuring the pH of a sample electrolyte, sample tissue, and the like. Such applications include medical applications in which the microscale pH sensor 10 is used to measure the pH of myocardial tissue, brain tissue, liver tissue, kidney tissue, lung tissue, and the like.

  In the exemplary embodiment of FIGS. 1 and 2, the pH sensor 10 includes a substrate 12, a first electrode 14, a second electrode 16, a system 18 for transporting bubbles, a closed fluid loop channel 20, a liquid boundary 22, a cover. 24, a plurality of connection pads 26a-26e, and a plurality of conductors 28a-28e (see FIG. 1).

  The substrate 12 can include, for example, any suitable type of material, i.e., a material that can undergo fabrication of various electrodes and other layers that it supports, for example. Suitable materials include, for example, silicon based materials (eg, silicon, glass, etc.), non-silicon based materials, polymeric materials (eg, polydimethylsiloxane or PDMS), and other materials. If the sensor is to be implanted in the body, the material can be, for example, biocompatible. In some embodiments, for example, the substrate 12 is a glass substrate. The first electrode 14 functions as an indicating or sensing electrode and may include, for example, any suitable type of material. In general, the material for the first electrode 14 exhibits a wide pH response range, high sensitivity, rapid response time, low potential drift, insensitivity to agitation, wide temperature operating range and wide operating pressure range. Is desirable.

  The first electrode 14 can include, for example, an ion selective field effect transistor (ISFET) or a metal oxide electrode. An ISFET is part of a solid state integrated circuit. ISFETs exhibit rapid response times (on the order of 1 millisecond) and are extremely rugged for in vivo applications.

  In the case of metal oxide electrodes, several metal oxides are suitable for use in the first electrode 14. The metal oxide can be deposited on a conductive (eg, metal) layer, for example, deposited or formed on the substrate 12. Metal oxide films or layers (eg, iridium oxide) are produced via various techniques including, for example, electrochemical oxidation via potential cycling, reactive sputtering, anodic electrodeposition, thermal oxidation, and others. be able to. In some embodiments, the first electrode 14 includes platinum and iridium oxide. For such embodiments, platinum can be deposited on the substrate 12 and iridium oxide can be formed or deposited on the platinum. According to another embodiment, the first electrode 14 includes chromium and iridium oxide. For such embodiments, chromium can be formed on the substrate 12 and iridium oxide can be formed on the chromium. According to another embodiment, the first electrode 14 includes titanium and iridium oxide. For such embodiments, titanium can be formed on the substrate 12 and iridium oxide can be formed on the titanium. The first electrode 14 is positioned in contact with the sample solution / electrolyte whose pH is to be measured (eg, within the sample tissue).

  The second electrode 16 functions as a reference electrode and may include any suitable type of material. Desirably, the reference electrode 16 maintains a constant or substantially constant potential in the electrolyte. In some embodiments, the second electrode 16 includes platinum and silver. For such embodiments, platinum can be formed or deposited, for example, on substrate 12, and silver can be formed or deposited on platinum. According to another embodiment, the second electrode 16 comprises platinum and silver chloride. For such embodiments, platinum can be formed or deposited, for example, on substrate 12, and silver chloride can be formed or deposited on platinum. According to other embodiments, the second electrode 16 includes chromium and silver. In such an embodiment, chrome can be formed or deposited on substrate 12, for example, and silver can be formed on chrome. According to other embodiments, the second electrode 16 comprises chromium and silver chloride. For such embodiments, chrome can be formed or deposited on substrate 12, for example, and silver chloride can be formed on chrome. According to another embodiment, the second electrode 16 comprises titanium and silver. In such an embodiment, titanium can be formed or deposited on the substrate 12, for example, and silver can be formed on the titanium. According to another embodiment, the second electrode 16 comprises titanium and silver chloride. For such embodiments, titanium can be formed or deposited, for example, on substrate 12, and silver chloride can be formed or deposited on titanium. The second electrode 16 is positioned in contact with a reference solution in the fluid closed loop channel 20.

  Foam transport system 18 and foams 30 and 32 operate as a fluid switch or controller 19 in conjunction with a liquid analyte 22 and a reference analyte solution in fluid channel 20. The fluid switch 19 is operable, for example, to turn the pH sensor 10 on or off. The fluid switch 19 can be any type of fluid switch suitable for providing a barrier between a fluid transport member, such as the liquid boundary 22, and a reference electrolyte. In some embodiments, the fluid switch 19 turns the pH sensor 10 (or another device) off and on, for example, by breaking the ionic electrical connection between the analyte solution and the reference solution. It is possible to operate. The fluid switch 19 can also be operable to reduce or eliminate mass transfer between the analyte solution and the reference solution.

  In some embodiments, as will be described in more detail below, the foam transport system 18 may use, for example, a dielectric electrowetting principle that provides switching functionality. According to various embodiments, the foam transport system 18 can include, for example, a plurality of electrodes. In the illustrated embodiment, the foam transport system 18 includes three electrodes 18a, 18b, and 18c. Foam transport system 18 may include any suitable type of material. In various embodiments, the foam transport system 18 includes platinum, an insulating layer (eg, silicon oxide, parylene, etc.), and a hydrophobic layer (eg, a fluorocarbon hydrophobic layer). In such embodiments, platinum can be formed or deposited, for example, on the substrate 12, and the insulating and hydrophobic layers can be formed or deposited on the platinum. According to other embodiments, the foam transport system 18 includes chromium, an insulating layer, and a hydrophobic layer. For such embodiments, chrome can be formed or deposited, for example, on the substrate 12, and the insulating and hydrophobic layers can be formed or deposited on the chrome. The foam transport system 18 is positioned in direct contact with the reference solution in the fluid closed loop channel 20.

  In the exemplary embodiment of FIGS. 1 and 2, the fluid channel 20 is a closed-loop channel 20 collectively defined by the substrate 12 and the cover 24. The fluid closed loop channel 20 can include, for example, any suitable type of ionically conductive aqueous solution. For example, according to various embodiments, the fluid channel 20 comprises a saturated potassium chloride solution. According to another embodiment, the fluid channel 20 comprises a saturated silver chloride solution. The fluid channel herein need not be a closed loop fluid channel. The fluid channel allows the movement of one or more bubbles, or if a bubble is generated within the channel, as described below, the fluid channel may have one or more bubbles desired. Allows displacement of the liquid so that it can be formed up to

  As shown in FIG. 1, in some embodiments, the fluid closed loop channel 20 surrounds the foam transport system 18 and includes a first foam 30 and a second foam 32. The first foam 30 is hydrodynamically connected to the second foam 32 via a saturated reference solution. Therefore, when the first bubble 30 is driven from the first position to the second position, the second bubble 32 moves from the third position to the fourth position. The third position is indicated by a solid line in FIGS. 1 and 2, while the fourth position is indicated by a broken line in FIGS. Thus, the first bubble 30 may be considered a “master” bubble and the second bubble 32 may be considered a “slave” bubble. The first and second bubbles 30 and 32 may comprise any suitable type of fluid material that is, for example, immiscible in the reference solution. At least the foam 32 can be immiscible in the analyte solution, for example. For example, according to various embodiments, the first and second bubbles 30 and 32 may include air, oil, a gas other than air (eg, hydrogen, oxygen, a mixture of hydrogen and oxygen, etc.), and the like.

  As used herein, the term “bubble” refers to a droplet or volume of one substance (fluid) in another fluid (reference electrolyte). The bubbles can be formed, for example, from a gas that is immiscible in the liquid in channel 20 (ie, a saturated reference solution) or a liquid that is immiscible in the liquid in channel 20.

  The liquid boundary 22 is positioned between the sample or analyte electrolyte and a reference solution (eg, saturated potassium chloride) encapsulated in the fluid closed loop channel 20, and between the analyte electrolyte and the reference solution in the fluid closed loop channel 20. Provides ionic electrical connection between. In some embodiments, the liquid boundary 22 is a member through which fluid transport can occur, and can include, for example, a porous or permeable material. For example, according to various embodiments, the liquid boundary 22 comprises a hydrophilic porous polymer. The porous material for the liquid boundary 22 can have a pore size of, for example, less than 1 micrometer. In some embodiments, the liquid boundary 22 is designed to limit or minimize mass exchange between the solution in the fluid closed loop channel 20 and the sample electrolyte (eg, for porous materials, By limiting the pore size). As shown in FIG. 2, the liquid boundary 22 is positioned between the substrate 12 and the cover 24 in the illustrated embodiment.

Cover 24 is connected to substrate 12 and cooperates with substrate 12 to define fluid closed loop channel 20. Cover 24 may include, for example, any suitable type of impermeable material. In the case of the implantable pH sensor 10, the cover 24 (and other components of the pH sensor 10 that contact the organism) can be, for example, biocompatible. For example, according to various embodiments, the cover 24 comprises glass or polydimethylsiloxane. Cover 24 may be connected to substrate 12 in any suitable manner. For example, according to various embodiments, the cover 24 is bonded to the substrate 12. In some embodiments where the cover 24 is glass and the substrate 12 is PDMS, the cover 24 is easily bonded to the substrate 12 simply by crimping together after surface O ₂ plasma treatment. . For example, if the fluid channel 20 width is relatively large (eg, about 1 mm or more), an adhesive can be used to bond the cover 24 to the substrate 12.

  As described above, in the illustrated exemplary embodiment of FIGS. 1 and 2, a plurality of connecting elements or pads 26a-26e are connected to the substrate 12 and may include any suitable type of conductor. For example, according to various embodiments, the connection pads 26a-e include platinum. According to another embodiment, the connection pads 26a-e include chrome. According to another embodiment, the connection pads 26a-e include titanium. According to another embodiment, the connection pads 26a-e include gold. The connection pad 26a is connected to the first electrode 14 through the conductor 28a. The connection pad 26b is connected to the second electrode 16 through the conductor 28b. Connection pads 26c, 26d, and 26e are connected to electrodes 18a, 18b, and 18c of foam transport system 18 via conductors 28c, 28d, and 28e, respectively. Connection pads 26a-e provide electrical connection of the first electrode 14, the second electrode 16, and the electrodes 18a, 18b, and 18c of the fluid switch 18 to one or more circuits external to the pH sensor 10. . As illustrated in FIG. 1, the first electrode 14 and the second electrode 16 may be connected to, for example, measurement electronics or circuitry 40, which may include, for example, a potentiometer circuit known in the art. Can do. The electrodes 18a, 18b, and 18c of the foam transport system 18 can be in electrical connection with, for example, control electronics or circuitry 50.

  The plurality of conductors 28a-e can be formed, for example, on the surface of the substrate 12, so as to connect the first electrode 14, the second electrode 16, and the electrodes 18a-c to the respective connection pads 26a-e. Function. As shown in FIG. 1 and described above, the first conductor 28a connects the first electrode 14 to the first connection pad 26a, and the second conductor 28b connects the second electrode 16 to the second electrode 16a. Connect to the connection pad 26b. Similarly, each individual conductor 28c-e connects the electrode 18a-c of the foam transport system 18 to a corresponding connection pad 26c-e, respectively. The conductors 28a-e may include, for example, any suitable type of conductive material. For example, according to various embodiments, conductors 28a-e include platinum. According to another embodiment, conductors 28a-e include chromium. According to another embodiment, conductors 28a-e include titanium. According to other embodiments, conductors 28a-e include gold.

  In the operation of the exemplary embodiment illustrated in FIGS. 1 and 2, the first electrode 14 is exposed to a sample electrolyte (or sample tissue). When the pH sensor 10 is in the off state (via the fluid switch 19), the first foam 30 is positioned on the “leftmost” electrode 18a of the foam transport system 18 (as viewed from the orientation of the figure), The second bubble 32 is positioned with respect to the liquid boundary 22. The positioning of the first bubble 30 and the second bubble 32 can be achieved, for example, in any suitable manner. For example, according to various embodiments, dielectric electrowetting techniques can be utilized to move the first bubble 30 and the second bubble 32 to their respective positions. In such an embodiment, sequential actuation of the “rightmost” electrode 18c and “intermediate” electrode 18b of the foam transport system 18 is utilized to place the first foam 30 and the second foam 32 in the off state of the pH sensor 10. Can be moved to their respective positions associated with.

  In the off-state position, the second bubble 32 forms, for example, a barrier over the second electrode 16 and the liquid boundary 22, and fluid / electricity between the sample electrolyte and the saturated solution in the fluid closed loop channel 20 ( The (ionic) connection can be effectively blocked, thereby reducing or preventing dissolution of the second electrode 16 in the saturated solution and reducing or preventing mass exchange through the liquid boundary 22. When the second bubble 32 is in the aforementioned off-state position, an immiscible phase interface (eg, a gas-liquid or liquid-liquid immiscible interface) is within or at the surface of the pores of the liquid boundary 22. , Formed between the second bubble 32 and the sample electrolyte. The interfacial tension between the phases (eg, between the gas phase and the liquid phase) operates to reduce or prevent leakage of the sample electrolyte into the fluid closed loop channel 20. Maintaining the pH sensor 10 in the off state extends the useful life of the pH sensor 10 compared to a sensor that is continuously maintained in the on state.

  When the pH level is measured, the pH sensor 10 is switched to the on state. In order to be switched on, the second bubble 32 is moved over the second electrode 16 and the liquid boundary 22 so as not to form a barrier, thereby saturating the sample electrolyte and the saturated solution in the fluid closed loop channel 20. It is possible to establish an electrical connection between them. According to various embodiments, the second foam 32, which is hydrodynamically connected to the first foam 30, moves the first foam 30 away from the “leftmost” electrode 18 a of the foam transport system 18. As a result, the second electrode 16 and the liquid boundary 22 are separated.

  The first bubble 30 may be separated from the “leftmost” electrode 18a of the bubble transport system 18 in any suitable manner. For example, according to various embodiments, the dielectric electrowetting principle is utilized to move the first bubble 30 and in turn cause the movement of the second bubble 32. In a dielectric electrowetting device or system, bubbles are transported by programming and sequentially operating an array of electrodes.

  In such an embodiment, activation of the “leftmost” electrode 18 a of the foam transport system 18 moves the first foam 30 from the “leftmost” electrode 18 a of the foam transport system 18 to the “rightmost” of the foam transport system 18. It operates to move toward the electrode 18c. Movement of the first bubble 30 towards the “rightmost” electrode 18 c of the bubble transport system 18 moves the second bubble 32 away from the second electrode 16 and the liquid boundary 22, thereby causing the second The barrier covering the electrode 16 and the liquid boundary 22 is removed. The removal of the barrier allows establishment of a fluid / electrical (ionic) connection between the sample electrolyte and the saturated solution in the fluid closed loop channel 20.

  In the manner described above, the pH sensor 10 can be quickly switched between off and on states with very low energy consumption. By forming a barrier covering the second electrode 16 and the liquid boundary 22 during the off state, and exposing the second electrode 16 and the liquid barrier 22 to the saturated reference solution of the fluid closed loop channel 20 only during the on state. The dissolution of the second electrode 16 and the mass exchange through the liquid boundary 22 is reduced or minimized, thereby extending the useful life of the pH sensor 10.

  As schematically illustrated in FIG. 1, at least one power source 60, such as a battery, can be provided for electrical connection with the sensor electronics 40 and the control electronics 50. The power source 60 can be used, for example, to power the sensor electronics 40, the control electronics 50, and the foam transport system 18 in the embodiment of FIG. In some embodiments, the pH sensor 10 communicates with a transceiver 52 (eg, via radio frequency or RF signal, eg, wirelessly), eg, externally connected, eg, in communication with control electronics 50. Via device 70 it can be operable and / or controllable. The control electronics 50 moves the bubbles 30 and 32, for example, as described above, so that the pH sensor 10 is in a number of predetermined time cycles and / or external signals (eg, the body in which the pH sensor 10 is implanted). Can be programmed (eg, via one or more programmed processors) to allow the pH to be measured. When the pH sensor 10 is activated or activated, the pH reading value is obtained by the sensor electronics 40. Sensor electronics 40 is in communication connection with control electronics 50 that provides control of foam transport system 18. Once the measurement is taken, the pH sensor 10 can be placed in an off state and deactivated via control of the foam transport system 18, as described above. The measured pH value is used, for example, for use (eg, for transmission outside the body via transceiver 52, or for use by another implanted system, which can include, for example, a treatment device). Can be made available for any).

  In some embodiments of the invention, the pH sensor includes a single bubble that provides a switch between an on state and an off state. For example, FIG. 3 shows that a single bubble 132 in channel 120 (formed between cover 124 and substrate 112) is used to form a barrier over second or reference electrode 116 and liquid boundary 122. FIG. 10 illustrates another exemplary pH sensor embodiment 110 operating as a fluid switch or controller 119 (as described with respect to pH sensor 10). As described above, by forming or creating a barrier over the liquid boundary 22, an off-state is created and between the analyte solution (contacting the first or indicator electrode 114) and the reference solution in the channel 120. Ionic electrical connections are broken or prevented. Further, in the off state, the bubble 132 reduces, minimizes or eliminates mass transfer between the analyte solution and the reference solution. The off state further reduces the dissolution of the electrode 116 in the reference solution. If the bubble 132 is of sufficient size to cover the electrode 116, dissolution (mass transfer) between the electrode 116 and the reference solution can be further reduced, minimized, or eliminated. Dissolution of the second electrode 116 and mass exchange through the liquid boundary 122 thus occur in a significant range only during the on state, thereby extending the useful life of the pH sensor 110.

  In the embodiment of FIG. 3, using an anode 142 and a cathode 144, bubbles 132, which are a mixture of oxygen and hydrogen, are positioned relatively close to each other (eg, within about 4 um in some embodiments). Generated through electrolysis. In the embodiment illustrated in FIG. 3, a foam transport system 118 (eg, a dielectric electrowetting system) is positioned on the upper surface of the fluid channel 120. The foam transport system 118 can include, for example, an array of electrodes 118a-e positioned on the inner surface of the cover 124 (ie, the upper surface of the fluid channel 120). In the illustrated embodiment, the electrolytic electrodes (ie, anode 142 and cathode 144) used to generate foam 132 are placed on substrate 112. To generate a bubble 132 (or a plurality of bubbles as discussed, for example, in connection with pH sensor 10 of FIGS. 1 and 2), for example, between about an anode / cathode pair such as anode 142 and cathode 144 A potential difference of 5V can be applied.

  During operation of the fluid switch 119, the foam 132 is first generated via electrolysis using the anode 142 and cathode 144 (see the rightmost dashed line in the fluid channel 120). The size of the foam generated can be controlled, for example, through control of the time that the potential is applied. To turn the fluid switch 119 off, the foam 132 is transported through the foam transport system 118 and covers the liquid boundary 122 (see the leftmost dashed line in the fluid channel 120), in some embodiments, The reference electrode 116 is covered. In order to turn on the fluid switch, the foam 132 is transported through the foam transport system 118 so as not to cover either the liquid boundary 122 or the reference electrode 116.

  FIG. 4 shows that a single bubble 232 in the channel 220 (formed between the cover 224 and the substrate 212) is described with respect to the pH sensor 10 of FIGS. 1 and 2 and the pH sensor 110 of FIG. Another exemplary pH sensor embodiment 210 used to form a barrier over the second or reference electrode 216 and the liquid boundary 222 and operating as a fluid switch 219 is illustrated. As described above, by forming or creating a barrier over the liquid boundary 222, an off-state is created, between the analyte solution (contacting the first or indicator electrode 214) and the reference solution in the channel 220. Ionic electrical connections are broken or prevented. If the bubble 232 is of sufficient size to cover the cover electrode 216, dissolution (mass transfer) between the electrode 216 and the reference solution can be further reduced, minimized, or eliminated.

  During operation of fluid switch 219, bubble 232 is first generated via electrolysis using anode 242 and cathode 244 (see the rightmost dashed line in fluid channel 220). As described above, the size of the generated foam can be controlled, for example, through control of the time that the potential is applied. To turn the fluid switch 219 off, the bubble 232 is generated to a size that covers the cover liquid boundary 222 and, in some embodiments, covers the reference electrode 216. Subsequently, in order to turn on the fluid switch, the bubble 232 uses the anode 242 and cathode 244 to reverse the electrolytic process so that neither the liquid boundary 222 nor the reference electrode 216 is covered. Size is reduced or completely eliminated. In order to provide foam reduction or elimination, a catalyst can be used to lower the energy barrier in the inversion process. In the case of bubbles 232, including hydrogen and oxygen bubbles, platinum (Pt) can be used as a catalyst, for example. In some embodiments, anode 242 and cathode 244 can be made to include a catalytic material, such as, for example, Pt. When a potential is applied to anode 242 and cathode 244, bubble 232 grows. When the potential is interrupted, the bubble 232 contracts. In an alternative embodiment, a catalyst source such as Pt can be provided separately from the anode 242 and the cathode 244.

  Fluid switches or controllers 19 of FIGS. 1 and 2, fluid switches or controllers such as 119 and 219 of FIG. 3, are, for example, porous members such as porous polymer members, permeable membranes or the like through which fluid can be transported. It can also be used in other devices where it is desirable to control fluid connections, ionic conduction, and / or mass transfer across the permeable member.

  FIG. 5 illustrates an embodiment of a system for taking a pH reading using a portable device and a multi-use sensing probe, according to an embodiment of the present invention. The system 300 includes a reader 310 and a disposable probe 350. In a typical configuration, the operation of the system 300 uses an indicator electrode (eg, an iridium oxide electrode) that is compared to a known potential generated by a reference electrode (eg, a silver-silver chloride electrode) in contact with the reference solution. Based on pH potentiometric measurements. One or more components of the system 300 are typically preconditioned to produce a known output, such as to avoid calibration steps during manufacture and / or use. The reader 310 includes a housing 315 with which a user interface 311 is integrated. The user interface 311 includes a display 313 and buttons 312. Display 313 is typically a liquid crystal or touch screen display that may display measured pH readings as well as system and other information. System information may include, but is not limited to, system readiness information, power level, alert or alarm condition information, current status of consumables, and combinations thereof. Other information provided by the system 300 via the user interface 311 includes environmental conditions such as temperature, humidity, and / or pressure information recorded by the sensor 317 of the reader 310 or the sensor 353 of the probe 350. obtain.

  The housing 315 further includes an electromechanical port that is configured to operatively engage the proximal end of the disposable probe 350. The probe 350 includes a housing 351, an indicator electrode assembly 370, and a liquid boundary 365. The liquid boundary 365 is typically constructed and arranged as described above with reference to FIGS. The indicator electrode assembly 370 includes a plurality of indicator electrodes, each of which is independently operable. In an exemplary embodiment, electrode assembly 370 is manufactured in a MEMS processing process, such as an iridium oxide electrode assembly manufactured in a MEMS process. In one embodiment, the electrode assembly 370 includes nine indicator electrodes as described with reference to FIG. 6 below. Numerous electrode configurations may be included, such as an array of 90 or more instructions and / or reference electrodes. Probe 350 also includes a reservoir 366 that stores a reference solution 367 and a reference electrode 360. Reference electrode 360 may be a silver / silver chloride reference electrode or another known reference source configured with a predictable pH sensitivity when contacted with a known reference solution. In one embodiment, the reference electrode 360 is an iridium oxide electrode. Alternative materials and combinations of materials can be used for the reference electrode 360, such as those described with reference to FIGS. Reference solution 367 may be a KCl solution or other suitable liquid used with reference electrode 360. Wires 361 and wire bundles 371 travel through housing 351 to port 316, such as to electrically connect reference electrode 360 and indicator electrode assembly 370 to electronics module 320, respectively. The module 320 included in the housing 315 of the reader 310 is configured to determine the pH level based on the electrical signals received on the wire 361 and the wire bundle 371 and display the pH information on the display 313. Is done. Module 320 is typically configured to automatically transition from the first indicator electrode to the second indicator electrode, such as to perform a second measurement after the first measurement. Module 320 may be configured to transition through multiple electrodes, such as through a look-up resistor that indicates the last electrode activated. The indicator electrode may be actuated or otherwise selected, such as by opening a membrane or other controllable orifice, as described in detail below. Module 320 may be further configured to interpret other information, such as signals received from sensor 353 and / or sensor 317. Module 320 may be further configured to store data, communicate with one or more external devices (eg, via wired or wireless communication), perform internal diagnostic checks, and the like. The stored data may include, but is not limited to, reference electrode 360 information, indicator electrode assembly 370 information, storage information, date of manufacture and other date information, and combinations thereof. When the liquid boundary 365 is saturated with the reference solution 367, it allows an electrical connection between the indicator electrode assembly 370 and the reference electrode 360 when the probe 350 is immersed in the sample solution. The probe 350 is a removable cap and may typically include a cap 352 that is a plastic material that attaches to the distal tip of the probe 350 and is removed prior to testing the sample solution. The cap 352 can be configured to prevent the liquid boundary 365 from drying out (eg, during storage or between uses) or otherwise protect the distal portion of the probe 350.

  The indicator electrode assembly 370 includes a plurality of indicator electrodes that are configured to be independently operable, such as for making a plurality of measurements using a single probe 350. These multiple measurements may be performed continuously, such as over a period of minutes to hours and / or over a longer period of time, such as weeks to months. User interface 311 is configured to allow an operator to individually activate each indicator electrode of electrode assembly 370, such as by electronics module 320 that issues one or more activation signals to assembly 370. A number of operable indicator electrode configurations may be employed, such as those described with reference to the following figures.

  The reader 310 is not shown, but is selected from the group consisting of a chamber configured to store a plurality of probes 350, a reservoir configured to store a reference solution 367, and combinations thereof. These additional components may be included.

  FIG. 6 illustrates a schematic diagram of an indicator electrode assembly comprising an array of pH indicator electrodes, according to an embodiment of the present invention. The indicator electrode assembly 370 comprises an array of indicator electrodes 375 (3 × 3 array as shown in FIG. 6). In an alternative embodiment, one or more indicator electrodes 375 can be configured as a reference electrode. Each electrode 375 is surrounded on the exposed surface by a membrane assembly 380. The membrane assembly 380 is configured to be operably operated to cover the indicator electrode 375 and to expose the indicator electrode 375 to the sample solution and the like. Operable operations include, but are not limited to, removal of membrane 381, rupture of membrane 381, separation of membrane 381, and combinations thereof. Membrane assembly 380 may be replaced with various other assemblies, such as various other electromechanical assemblies configured to operably provide an opening between the first volume and the second volume. obtain. The indicator electrode assembly 370 includes a multi-layer structure so that conductors, insulators, and other functional elements can be assembled to the substrate as described with reference to FIG. 7 below. One layer comprises electrical traces 377, each terminating at a first end to indicator electrode 375 and a second end to connection pad 379. In one embodiment, the indicator electrode 375 is fixed to the mounting pad 373 and the trace 377 is attached to the mounting pad 373. Trace 377 and pad 379 are configured to transmit electrical information, such as voltage or other indicator electrode 375 information, to a separate device, such as reader 310 of FIG. Another layer of assembly 370 includes traces 385 and 386 to connect connection pads 383 and 384 to membrane assembly 380. Traces 385 and 386 and connection pads 383 and 384 are configured to provide power (eg, positive voltage and ground) to membrane assembly 380. In one embodiment, connection pads 379, 383 and 384 connect to a wire bundle, such as wire bundle 371 in FIG. Traces 377 and pads 373 and 379 may be made using a titanium deposition and etching process. All traces may comprise other suitable electrically conductive materials such as gold, platinum, copper, aluminum, and / or silver. Although the array 370 is shown with nine indicator electrodes 375, a number of electrode configurations may be included, such as an array of 90 or more indicator and / or reference electrodes.

  FIG. 6a illustrates a detailed view of an openable membrane assembly according to an embodiment of the present invention. The membrane assembly 380 includes a heating element 382 and a membrane 381. Traces 385 and 386 connect electrical connection pads 383 and 384 to heating element 382, respectively. In another embodiment (not shown), the plurality of membrane assemblies 380 have individual signal pads 383, but share a common ground pad 384 'and the trigger of any individual pad 383 is connected to the assembly. 380 is ruptured. The heating element 382 can be constructed using a gold deposition and etching process to leave a high resistance pattern that is configured to generate heat when a current is applied. The deposition and etching process may include additional steps and materials such that the heating element 382 is deposited within the film 381 (eg, within one or more layers of the film 381).

  In FIG. 6a, the heating element 382 is within, in contact with and / or in the membrane 381, such that actuation of the heating element 382 causes a physical change in the membrane 381, and fluid can pass through the membrane 381. Can be constructed in close proximity. This physical change, such as film tearing caused by the thermal force generated by the heating element 382, causes the fluid to flow into a previously sealed chamber, as described below with reference to FIG. Can be possible.

  FIG. 7 illustrates a cross-sectional view of an array of indicator electrodes included in an indicator electrode assembly, according to an embodiment of the invention. The indicator electrode assembly 370 includes a plurality of chambers 369 surrounded by a wall 378 and a cover 368. Cover 368 is constructed and modified electronically, such as to open chamber 369 to the ambient environment (eg, exposure to sample solution), etc., as described with reference to FIG. 6a above. A membrane assembly 380 is provided. The indicator electrode assembly 370 also includes a support material 374 surrounded by a casing 376. The chambers 369 each surround individual indicator electrodes 375 that are deposited on the electrode mounting pads 373. In one embodiment, the mounting pad 373 is constructed from titanium, such as titanium, that is deposited in a deposition process. The indicator electrode 375 typically includes an iridium oxide (IrOx) electrode. Indicator electrode 375 may also comprise other materials suitable for electrically measuring the pH of the sample solution. The components of the indicator electrode assembly 370 are constructed on a substrate 372, typically a glass, silicon or plastic substrate. An exemplary fabrication process for manufacturing the indicator electrode assembly 370 is described in detail with reference to FIG. 9 below. Array 370 is shown with three indicator electrodes 375, but numerous electrode configurations are included in various square, rectangular, and other geometric configurations, such as an array of over 90 indicator and / or reference electrodes. obtain.

  Referring now to FIG. 7a, the membrane assembly 380 of FIG. 7 is modified so that an opening in the cover 368 'is created between the chamber 369 and the ambient environment. After the opening is created and the indicator electrode assembly 370 is placed in the sample solution, only the indicator electrode (shown as indicator electrode 375 'in FIG. 7a) positioned under the cover 368' is the sample solution. Will be exposed to. In one embodiment, one or more chambers 369 are constructed as a vacuum chamber such that when the membrane assembly 380 ′ (corresponding to cover 368 ′) is modified, the sample solution is drawn into chamber 369. . A vacuum chamber is typically created by manufacturing chamber 369 and its surrounding walls in a vacuum environment. In addition or alternatively, the walls of one or more chambers 369 may be shaped or include one or more coatings (eg, hydrophilic coatings), such as to draw a sample solution into chamber 369. obtain. Additionally or alternatively, the structural wall material can be hydrophilic or otherwise constructed and arranged to draw the sample solution into the chamber 369.

  FIG. 8 illustrates an indicator electrode assembly according to an embodiment of the present invention. The indicator electrode assembly 370 is typically constructed and arranged with components similar to the indicator electrode assembly 370 of FIGS. 7 and 7a. The indicator electrode assembly 370 of FIG. 8 further includes a vent 364 positioned in the substrate 372 between the chamber 369 and the opposite surface of the substrate 372. Vent 364 is configured to improve transport of sample or other solution into chamber 369. Although the array 370 is shown with three indicator electrodes 375, a number of electrode configurations may be included, such as an array of 90 or more indicator and / or reference electrodes.

  Referring now to FIG. 8a, the membrane assembly 380 of FIG. 8 is modified such that the cover 368 ′ is opened through operation of the membrane assembly 380 ′ as described with reference to FIG. 7a above. ing. Chamber 369 is typically exposed to its surrounding environment, such as a sample solution. The pressure increase caused by the inflow of fluid into chamber 369 is mitigated through vent 364. In one embodiment, vent 364 is not shown, but may be operably attached to a negative pressure source, such as a vacuum pump, configured to draw sample solution into open chamber 369.

  FIG. 9 illustrates a step-wise process for manufacturing an array of indicator electrodes, according to an embodiment of the invention. In an exemplary embodiment, steps 410 through 412 are performed as a continuous group, and steps 420 through 422 are also formed as a continuous group. Step 410 shows the substrate 372 with a titanium mounting pad 373. A mounting pad 373 is mounted on the substrate 372 using a deposition and etch process, typically using an E-beam evaporator and photolithography, and typically depositing a patterned layer of titanium onto the substrate. Generate on 372. Photolithography and etching processes remove a portion of the deposited layer, leaving the mounting electrode 373 as shown.

Step 411 is typically made of SiO _2, includes a wall 378, showing the assembly of step 410. Wall 378 is deposited on substrate 372 by a curing and etching process after the deposition process to achieve the configuration shown.

  Step 412 here shows the assembly of step 411 including the indicator electrode 375. The electrode 375 typically comprises an iridium oxide pad deposited directly on the mounting electrode 373. After deposition of the electrode 375, heat treatment, voltage treatment (voltage treatment, including application of a known voltage to the iridium oxide layer in the presence of a buffer solution), or chemical treatment (eg, to a chemical solution for a certain period of time). Post-fabrication processes can be performed that include one or more of (exposure). The voltage is applied for a fixed time at a constant or variable level to modify the chemical composition of the iridium oxide layer. When exposed to a reference solution, this voltage correction can be used to cause the electrode to produce a known voltage response to the pH of the reference solution, such as to avoid calibration.

  Step 420 shows a support material 374, typically a silicon wafer, encapsulated by a casing 376, typically a silicon nitride casing. Both casing 376 and support material 374 are etched to create a recess in support material 374 for chamber 369.

  Step 421 shows the assembly of step 420 including cover material 368 deposited on casing 376 and chamber 369. Membrane assembly 380 is positioned within cover material 368. The membrane assembly 380 typically includes a silicon nitride layer (eg, an upper portion of the cover material 368 proximate the membrane assembly 380), a gold and chromium layer configured as a heating element, and a second layer of silicon nitride. (E.g., the bottom portion of cover material 368). The two silicon nitride layers of the membrane assembly 380 function as a membrane that can be controllably manipulated by actuation of the heating element.

  Step 422 shows the assembly of step 421 after an etching process has been performed and a portion of casing 376 covering the top of chamber 369 has been removed.

  Step 430 shows the assembly of steps 412 and 422 joined together. Cover material 368 is typically bonded to wall 378 using an anode or similar bonding process.

  Step 431 shows the final indicator electrode assembly 370. A final wet etch process is performed to remove the support material 374 from above the cover 368 and expose the membrane assembly 380.

  Although the array 370 of FIG. 9 is shown with three indicator electrodes 375, a number of electrode configurations may be included, such as an array of 90 or more indicator and / or reference electrodes.

  FIG. 10 illustrates a cross-sectional view of an alternative embodiment of an array of electrodes, according to an embodiment of the present invention. The array 370 'includes at least one indicator electrode 375 and at least one reference electrode 360'. Indicator electrode 375 is typically constructed and arranged to include similar components of one or more of indicator electrodes 375 of FIGS. The indicator electrode 375 can be manufactured as described with reference to FIG. 9 above.

  Reference electrode 360 'is not shown but is configured to cooperate with indicator electrode 375 or another indicator electrode that is integral with array 370 to provide a reference signal. Reference electrode 360 ′ and one or more of its components (eg, walls, chambers, conductive pads and traces, membrane assemblies, etc.) are one similar to that described with reference to FIG. 9 above. It can be manufactured in the above process.

  The reference electrode 360 ′ is typically attached to the substrate 372 via a mounting pad such as a titanium mounting pad 373 ′. Chamber 362 surrounds the surface of electrode 360 '. The cover 368 includes a membrane assembly 380 'positioned between the chamber 362 and the second chamber, the reservoir 366'. The membrane assembly 380 'is configured to be operably operated, such as to expose the reference electrode 360' to the reference solution 367. Operable operations include, but are not limited to, removal of a portion (eg, membrane) of membrane assembly 380 ', rupturing membrane assembly 380', separation of membrane assembly 380 ', and combinations thereof. The operable operation of the membrane can be accomplished through the application of one or more forces to the membrane. Typical force applications include, but are not limited to, activation of heating elements in, on, or close to the membrane, application of pressure, such as a reference solution pressure, to the membrane, foam formation by electrolysis on the membrane (see FIG. 3 above). Application of pressure, such as atmospheric pressure, formed by (as discussed above) and combinations thereof. Membrane assembly 380 ′ replaces various other assemblies, such as various other electromechanical assemblies configured to operably provide an opening between the first and second sections. Can be. Support material 374 surrounds chamber 362 and reservoir 366 '. Support material 374 is surrounded by casing 376.

  A liquid junction, contact 365 ′, is positioned between chamber 369 and chamber 362. The liquid boundary 365 'is typically constructed and arranged as described with reference to Figures 1-5 above. In an alternative embodiment, the virtual liquid boundary 365 ′ is a co-pending application filed on the same day as Clark et al. The disclosure may be used as described in (herein incorporated by reference in its entirety).

  Referring now to FIGS. 10a and 10b, exemplary operation of the array 370 'of FIG. 10 is illustrated. In FIG. 10a, the membrane assembly 380 'is actuated via one or more wires or the like not shown, but described in detail with reference to FIGS. 6 and 6a above. The reference solution 367 flows into the chamber 362 'and contacts the reference electrode 360' and the liquid boundary 365 '. In FIG. 10b, the membrane assembly 380 is actuated via one or more wires or the like as described above. The sample solution is in contact with the indicator electrode 375 and the liquid boundary 365 ′ so that the signals from the indicator electrode 375 and the reference electrode 360 ′ can be interpreted by a reading device, as described with reference to FIG. 5 above. Can be done.

  The array 370 of FIGS. 10, 10a, and 10b is shown with a single indicator electrode 375 and a single reference electrode 360 ′, but an array of nine or more, 30 or more, or 90 or more indication and / or reference electrodes A number of electrode configurations can be included. In FIG. 10c, the array 370 '' includes two reference electrodes 360a and 360b and five indicator electrodes 375a-375e. In an exemplary embodiment, the single reference electrode 360a or 360b is configured to take multiple readings, such as to provide a reference to multiple indicator electrodes 375a-375e.

  As shown in FIG. 10 c, the array 370 ″ can include one layer with electrical traces 377, each with a first end to the indicator electrodes 375 a and 375 b and a connection pad 379. And the second end. In one embodiment, the indicator electrodes 375a and 375b are secured to the mounting pad 373 and the trace 377 is mounted pad 373 (the mounting pad 373 is not shown, but as shown in FIGS. 10, 10a and 10b above, It is mounted directly under the electrode). Trace 377 and pad 379 are configured to transmit electrical information, such as voltage or other indicator electrode information, to a separate device, such as reader 310 of FIG. Another layer of assembly 370 ″ includes traces 385 and 386 to connect connection pads 383 and 384 to membrane assembly 380. Traces 385 and 386 and connection pads 383 and 384 are configured to provide power (eg, positive voltage and ground) to membrane assembly 380. In one embodiment, connection pads 379, 383, and 384 connect to a wire bundle, such as wire bundle 371 in FIG. Traces 377 and pads 373 and 379 may be made using a titanium deposition and etching process. All traces may be made of other suitable electrically conductive materials such as gold, platinum, copper, aluminum, and / or silver. Array 370 '' is shown with five indicator electrodes 375a-e, but many electrode configurations may be included, such as an array of 90 or more indicator and / or reference electrodes.

  The foregoing description and accompanying drawings describe a number of examples of representative embodiments at the present time. Various modifications, additions and variations in design will be apparent to those skilled in the art in light of the above teachings without departing from or exceeding the spirit of the invention. Is determined based on the description of the scope of claims, not the above description. All changes and modifications belonging to the wording scope of the present invention described in the claims and equivalents thereof are included in the scope of the present invention.

Claims (52)

A system for obtaining pH measurements,
A disposable probe comprising a plurality of indicator electrodes and at least one reference electrode;
A reader operatively engaged with the disposable probe and constructed and arranged to provide sample pH information.   The system of claim 1, wherein the disposable probe further comprises a plurality of controllable orifices.   The first orifice is constructed and arranged to provide a first fluid path to the first indicator electrode, and the second orifice is constructed and arranged to provide a fluid path to the second indicator electrode. The system of claim 2, wherein the system is arranged.   4. The system of claim 3, further comprising an electronics module constructed and arranged to actuate the first controllable orifice and subsequently actuate the second controllable orifice. .   The system according to claim 4, wherein the reader comprises at least a part of the electronic device module.   The system of claim 4, wherein the electronics module comprises a look-up table that includes controllable orifice actuation information.   A first orifice is constructed and arranged to provide a first fluid path to a first indicator electrode, and a second orifice is constructed to provide a fluid path to the at least one reference electrode The system of claim 2, wherein the system is arranged.   The system of claim 2, wherein the at least one controllable orifice comprises a membrane.   The system of claim 8, wherein the film comprises a multilayer film.   9. The system of claim 8, wherein the membrane comprises a heating element that is constructed and arranged to create an opening in the membrane.   The system of claim 10, wherein the heating element comprises a heating coil.   The system of claim 10, wherein the heating element comprises one or more of gold or chrome.   The system of claim 10, wherein at least a portion of the heating element is positioned within the membrane.   The system of claim 10, wherein at least a portion of the heating element is positioned in contact with the membrane.   The system of claim 8, wherein the at least one orifice is manufactured in a MEMS process.   The system of claim 8, further comprising a reference solution, wherein at least one orifice is positioned between the reference solution and the reference electrode.   The system of claim 16, wherein the reference electrode is configured to provide pH information for a plurality of samples.   The system of claim 1, wherein the at least one indicator electrode comprises an iridium oxide electrode.   The system of claim 1, wherein the plurality of indicator electrodes comprises at least nine indicator electrodes.   The system of claim 1, wherein the plurality of indicator electrodes comprises at least 90 indicator electrodes.   The system of claim 1, wherein the plurality of indicator electrodes further comprises at least three indicator electrodes, and the disposable probe further comprises at least a second reference electrode.   The system of claim 1, further comprising a walled chamber surrounding at least one indicator electrode.   The system of claim 22, wherein the walled chamber comprises a vacuum chamber.   24. The system of claim 22, further comprising one or more vents in fluid communication with the walled chamber.   23. The system of claim 22, wherein the walled chamber comprises a hydrophilic coating.   The system of claim 22, wherein the walled chamber is made of a hydrophilic material.   23. The system of claim 22, wherein the walled chamber is constructed and arranged to draw a sample solution into the walled chamber.   The system of claim 1, further comprising a mounting pad and a substrate, wherein the at least one indicator electrode is fixedly attached to the mounting pad, and the mounting pad is fixedly attached to the substrate.   30. The system of claim 28, wherein the mounting pad comprises a titanium mounting pad.   The system of claim 1, wherein the at least one indicator electrode is manufactured using a MEMS process.   The system of claim 1, wherein the at least one reference electrode comprises a silver-silver chloride reference electrode.   The system of claim 1, wherein the at least one reference electrode comprises an iridium oxide reference electrode.   The system of claim 1, wherein the at least one reference electrode comprises at least two reference electrodes.   The system of claim 1, wherein the at least one reference electrode comprises a silver-silver chloride reference electrode.   The system of claim 1, wherein the reader comprises a user interface.   The system of claim 1, wherein the reader comprises an electronics module.   The system of claim 1, further comprising a liquid boundary.   38. The system of claim 37, further comprising a cap configured to prevent drying from the liquid boundary.   The system of claim 1, further comprising a reference solution.   40. The system of claim 39, wherein the reference solution comprises a KCl solution.   The system of claim 1, further comprising a substrate, wherein at least one of the at least one indicator electrode or the at least one reference electrode is positioned on and / or proximate to the substrate.   42. The system of claim 41, wherein the substrate comprises a material selected from the group consisting of glass, silicon, plastic, and combinations thereof.   42. The system of claim 41, wherein the at least one reference electrode is positioned on and / or proximate to the substrate.   42. The system of claim 41, wherein at least three indicator electrodes and at least two reference electrodes are positioned on and / or proximate to the substrate.   45. The system of claim 44, wherein at least one of the two reference electrodes is configured to work in cooperation with at least two indicator electrodes.   The system of claim 1, further comprising a sensor.   49. The system of claim 46, wherein the sensor is selected from the group consisting of a temperature sensor, a humidity sensor, a pressure sensor, and combinations thereof.   48. The system of claim 46, wherein the reader comprises the sensor.   48. The system of claim 46, wherein the disposable probe comprises the sensor.   The system of claim 1, further comprising a second disposable probe.   A system as described with reference to the previous figure.   A method as described with reference to the previous figure.